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i've been reading a lot about HIV in the last few weeks, and one thing I haven't explained yet is why the viral load can go from 200000 to < 50 but still cannot be completely gone? I understand that there are copies that hide in the lymphs, but then where did the 199950 others go? Are they killed? Eliminated via urine? Eaten by T8? And why are the 50 left are not eliminated?

I remember my doctor saying that the VL is exponential, so 200000 to 100000 is "a few less" but 200000 to 40 is "really a lot", so what's not working for the last 40? Is it possible that some people that have been undetectable for years with a stable CD4 are free from the virus?

It isn't just 50 or 49, it's a number less than 50...just not zero. It is less than 50 because the current tests can't measure below 50 copies per unit of measure. (I just know JK or newt is going to come in here and explain this so much better than I am, but I hope this helps some anyway.)

I have wondered about the same possibility about people who are undetectable for a long time with stable CD4s...might they actually be free and clear and it's just that nobody knows it? Everybody is assuming it is still there in small amounts, but it is really gone? But I think it has been fairly established that there are reservoirs where the virus hangs out dormantly. So the net effect is that it is said that your VL is <50...but not zero. Because it is known that there are some copies here and there that are lurking in wait. (BTW- the meds are effective only on copies of the virus that are in replication mode- trying to copy themselves. The meds don't change the virus, but change your body- making it inhospitable to that process.)

Did that help at all?

PS- I don't consider that a basic question. I consider that indicative of someone actively seeking to understand this infection. I'll bet some others on here will come along with some really kick-ass explanations in awhile.

(BTW- the meds are effective only on copies of the virus that are in replication mode- trying to copy themselves. The meds don't change the virus, but change your body- making it inhospitable to that process.)

So then what is the Viral Load counting? Can't be infected Tcells, or then I don't understand how you can have a VL of 30000 and a CD4 of 400. Isn't the VL counting all the floating ones that have not bound to the CD4 yet?

Yes, and I am afraid I am going to fail you here with providing a crystal clear explanation of this. What does Ann say? It just is, ok? LOL

Amounts of active virus and CD4's are not directly proportional. The amounts (well, I guess being blood borne) are fluid. As in, VL of 100,000 and CD4 count of 300 doesn't mean that a VL of 200,000 will automatically equal CD4 counts of 150 or a VL of 50,000 with a CD4 of 600. There can be clusters or clumps of virus, CD4s, hormones or other bloodly things moving through your system at any given time. I think of it as like, say....if you've ever stared at a stream and seen a little cluster of leaves or bubbles drifting down through it. If you sampled the stream here, a lot of leaves and bubbles. Just up stream? Not so much. Gosh, this is kinda hard for me to describe!

But anyway, the VL test is tracking copies of active virus in your system.

Your body is constantly trying to make more CD4s and other necessary body things and channel them out through your system. HIV is constantly trying to make more HIV and channel that out through your system. All kinds of things- from other infections, blood levels of meds to foods you have consumed (or not) can move blood levels of hormones, sugars, fats, VL and CD4s and everything else up or down depending.

HIV is constantly trying to make more HIV and channel that out through your system.

No HIV is a retro-virus, it has no brain unless it's swallowed by a CD4 by means of protein slurping. It's the CD4 that gets tricked by the proteins that surround the HIV cell's membrane, and unfortunately there is "binding" that allows the RNA to enter the cell, which disturbs the cell's DNA processus and ends up using the virus' RNA to build its DNA, which turns it into a virus duplicator. If i'm wrong in this statement, feel free to let me know, this is what I understood by reading about it, I could be completely off.

All kinds of things- from other infections, blood levels of meds to foods you have consumed (or not) can move blood levels of hormones, sugars, fats, VL and CD4s and everything else up or down depending.

Is this helping?

Of course it's helping. I'm fascinated by this. And I agree, whatever else happens in your body at the same time must have a deciding effect on how your overall immune system is working. And i'm sure we only know the tip of the iceberg.

Yeah, I know that HIV is a retrovirus and doesn't have a brain. I was just trying to paint a simple kind of picture in an effort to maybe help you understand the whole fluctuation thing. Kinda like "protein slurping"...which I am pretty sure isn't a medical term!

I'm really hoping for the resident brainiacs on here to step in a illuminate this in better terminology than I can offer. The problem I have is that I think this was all explained in simplistic (and not entirely accurate) terms to me when I asked these very questions. Thus, I am only able to talk about it on a certain level myself.

I believe you are right and I misspoke about the VL measuring "active" VL. In that instance, I was meaning the virus that is floating around the system waiting to attach to a CD4...not the ones laying dormant in the lymphs and stuff. By "active", I meant moving around in the system there. See? I can get tricky to talk about. Gotta watch my words.

You are right. This is a terrific thread that deserves to be widely seen and discussed. We will all do well to learn to understand this process better and be armed to communicate it better to others. We owe ourselves that. And sadly, even in our most basic discussion so far here, I think we already understand it a lot better than most people I see at the IDP. Most don't seem to know- worse, care how this all happens in our bodies. I sure do. I look forward to this thread growing.

If it doesn't catch the appropriate notice, we should conspire to keep bumping it til it does!

Yeah, I know that HIV is a retrovirus and doesn't have a brain. I was just trying to paint a simple kind of picture in an effort to maybe help you understand the whole fluctuation thing. Kinda like "protein slurping"...which I am pretty sure isn't a medical term!

I'm really hoping for the resident brainiacs on here to step in a illuminate this in better terminology than I can offer. The problem I have is that I think this was all explained in simplistic (and not entirely accurate) terms to me when I asked these very questions. Thus, I am only able to talk about it on a certain level myself.

I believe you are right and I misspoke about the VL measuring "active" VL. In that instance, I was meaning the virus that is floating around the system waiting to attach to a CD4...not the ones laying dormant in the lymphs and stuff. By "active", I meant moving around in the system there. See? I can get tricky to talk about. Gotta watch my words.

You are right. This is a terrific thread that deserves to be widely seen and discussed. We will all do well to learn to understand this process better and be armed to communicate it better to others. We owe ourselves that. And sadly, even in our most basic discussion so far here, I think we already understand it a lot better than most people I see at the IDP. Most don't seem to know- worse, care how this all happens in our bodies. I sure do. I look forward to this thread growing.

If it doesn't catch the appropriate notice, we should conspire to keep bumping it til it does!

great post, thunter34, you're obviously as curious as I am and eager to understand all this. Can't wait to get expert answers!

The measurement of viral load is copies of the virus per milliliter of blood (copies/mL). So, a viral load of 50 copies represents a shed load of virus still. But not enough for it to replicate and damage your CD4s. Plus, the measurement is for peripheral blood, not for other parts of the body eg semen, CNS fluid.

The virus is mainly eliminated from the body by your immune system cleaning up infected cells, rather than directly, which is why you tend to get a massive drop at the beginning of treatment.

Combo stops the virus replicating, rather than destroying it (technically you might say it's virostatic, ie makes the virus stand still). Which means it has to be replicating to be amenable to treatment, and therefore non-replicating virus (latent or resting ... such a Hollywood actor, HIV) hiding out in various parts of your body (reservoirs) can't be tackled with current treatment.

Hope this helps

- matt

Now playing: Joan As A Police Woman, Real Life << edited to get this right

Yeah, sort of. I believe it means that if you checked your regular VL against a semen sample from yourself, you'd get different numbers. Which is why I don't know that I completely buy into that idea that being on meds makes one less infectious to partners (as is frequently batted around). You may have an undetectable VL based on blood draws. That does not mean that the amount of virus present in your semen is undetectable. The testicles is another area like the brain that the meds have a difficult time penetrating and effecting. This is another thing that makes me worry about long-term psychological effects of HIV infection (fodder for another thread, no doubt). Is there some crazy in our futures? The virus is able to continue replicating a lot more freely in the brain- what impact does that have long term?

being on meds definately makes you less infectious to partners, in fact in a new study release in last month 200 sero opposite st8t couples were followed they all created babies and none wore condoms and none of the partners got HIV, this is because they were all undetectable, so the advice was st8t couples can have unprotected sex to concieve a child but best to have protected sex during the days women is not fertile, i think this is a HUGE HUGE HUGE event, and i dont know but i think there is still a huge bias against gay male sex as opposed to st8t sex, for example, st8ts live swim in a world of love being the glue of thier culture, a man loves a woman visa versa and even though one is poz other neg, they stick together and scientists now prove they dont transmit even if they have sex without a condom in order to create a baby, (personally if i was neg i would be afraid, but the point is love, they love and want to have baby with that person)

gays swim, live in a world of sex, where love is infinately less important, so now we have all these fear campaigns... isolate the poz guys bilboard where they toute this... meanwhile in st8t world they are having babies one poz undetectable one neg...!!!!!!!!!!!!!!!!!!!!

there are different compartments the virus is in, brain, genital tract, and blood etcthe measure is only in blood, there are billions of cd4s created every day and only one in a million is infected

i cannot find the article about sero opposite st8t couples but it listed over 200 participants and they recommended condomless sex to concieve a baby if poz partner is undetectable

No offense, bimazek...but there's a lot about your post that I'm confused by and question.

Yes, there is a bias against gay sex in the world at large. No big secret there, but biologically gay sex does not equate directly to gay sex. Penis in anus is a different physical event than penis in vagina- and the potential for transmission reflects that. Maybe I am misreading your post a bit.

I'm also hanging quite a bit on the "love is infinitely less important" line about gays. I'd argue that one. I think the desire to love and be loved is a fairly universal human characteristic. I think the reasons behind different sexual patterns (which I believe you are alluding to) are rather complex.

Anyway, I may just be misinterpreting your post. Sorry to the milker if we are Amtraking a bit. We'll steer it back on track.

being on meds definately makes you less infectious to partners, in fact in a new study release in last month 200 sero opposite st8t couples were followed they all created babies and none wore condoms and none of the partners got HIV, this is because they were all undetectable, so the advice was st8t couples can have unprotected sex to concieve a child but best to have protected sex during the days women is not fertile

Please quote the study and do not say "definitely" and "because". There are plenty of cases of HIV positive babies. And you're mixing low viral count with menstrual cycle without explaining which one may have an effect on the non-proliferation of the HIV virus.

gays swim, live in a world of sex, where love is infinately less important

I can assure you that straight men (and women!!) are as obsessed with sex as gay men and that there are countless gay men who are more faithful than straight couples. I am one of them when i'm in a relationship, never cheated in my life. I don't know where you got the idea that gay men "swim, live in a world of sex" in opposition to straight couples?

there are different compartments the virus is in, brain, genital tract, and blood etcthe measure is only in blood, there are billions of cd4s created every day and only one in a million is infected

Yes but what thunter was asking was if there would be a higher concentration in sperm than in blood that would not be measured by normal tests and may actually make the "undetectable" test not a basis for "safer" unprotected sex.

There was an article just recently about HIV reservoirs in the genitalia. Also one about the gut. Wish especially that I could find the one about the genitalia . Will keep hunting.

EDITED: As much as I dislike using The Body, here is a referene link to a (very) small article about the testicle reservoir dealie. Searches on POZ don't pull it up (though I am sure that is where I originally read about it). You might need to scroll down a bit to see the article.

Hi All, Great thread. This question has bugged me ever since i found out my South African girlfriend was diagnosed with AIDS...Still don't quite understand how the meds drop the VL so dramiatically.. Where does the copies go when on the meds. From what i'm reading, they don't'die' but are cleared away by uninfected CD4s. ?? So, how come those uninfected CD4s can take on HIV and win?

Also, so much effort underway on finding the vaccine which is great but why so little on finding the cure. LOts of vaccine trials but i can find very little on AIds cure when i google it except Presiden Jammah of Gambia who says he has a cure but wont tell anyone what it is !!!!!

Hi All, Great thread. This question has bugged me ever since i found out my South African girlfriend was diagnosed with AIDS...Still don't quite understand how the meds drop the VL so dramiatically.. Where does the copies go when on the meds. From what i'm reading, they don't'die' but are cleared away by uninfected CD4s. ?? So, how come those uninfected CD4s can take on HIV and win?

Also, so much effort underway on finding the vaccine which is great but why so little on finding the cure. LOts of vaccine trials but i can find very little on AIds cure when i google it except Presiden Jammah of Gambia who says he has a cure but wont tell anyone what it is !!!!!

OK- this post brings up another area about this where I am also a bit confused. The question of how come those uninfected CD4's can take on HIV and win? The answer I was given was essentially that your body does have some fighting power against HIV (hence the anti-bodies by which an HIV test determines positive or negative, ya know...they don't test for virus, they test for antobodies TO the virus that the body has started producing in response to its presence). The problem (as it was explained to me) is that HIV replicates itself faster than the body can clear it out.

Say...in a day, the body took care of 1,000 copies of the virus. But in that same day, HIV managed to make 50,000 copies of itself in that same time. Eventually, the body is taken over by the sheer weight of numbers.

Here is a bit more on that:

You hear about CD4's and CD8's and so on, right? I was told that these different cells have different functions and "rank", if you will, within the immune system. Think of soldiers and generals, ok? Again- AS I WAS TOLD- the body can fight off HIV in theory, but different cells rely on the CD4's as the generals to tell them to do so. Over time, there aren't enough of these "generals" around in the system to command an attack on the virus...because of that outpacing I mentioned. So after awhile, whatever fight the body may have been attempting just collapses altogether.

Again...this is how it was explained to me, and I may be WILDLY incorrect with this description. But that scenario does make a kind of sense to me. It explains a lot. What say you folks?

PS- I love this thread. It is a good example of how dialogue about HIV issues can move on here. I may be completely incorrect about my explanations, but I still feel safe in sharing what I have been told as we try to come to understand how this all works...and confident that anything that needs clarification or correction will eventually get it here.

The question of how come those uninfected CD4's can take on HIV and win?

Usually when a virus enters the body it binds to the b-cells, which eats it, then release a protein that attracks the cd4 tcells (simply explained cd4 t-cell just means that this is a cell that has been created in the Thymus, as opposed to b-cells coming from the Bone marrow, and is covered with a protein called CD4). The cd4 then binds to the b-cell, which in turn release a signal indicating to the b-cell that it should start create antibodies given the "image" that it just ate. Antibodies are just proteins that bind to the virus and the result is that the virus cannot bind back to the cells.

All of this would be fine, except that the virus also binds to cd4 t-cells, which are not programmed the same way as the b-cells. Once the virus is bound to a cd4 t-cell, it releases enzymes that allows it to enter the cell and disturb it. From that point, the cd-4 is not only not operational anymore, but it also serves as a home for the virus to replicate. There are no natural mechanisms to stop this, so that's why the virus is able to replicate faster than if it was just binding to a b-cell. Fortunately the cd-4 t-cell finally dies.

Current meds disturb the mechanism of the virus entering the cd-4 t-cell, or prevent its replication once in the cd-4 t-cell. New meds being studied try to completely block entry.

Where do the live viruses go? They "float" in your body, but they're inactive if they have been "caged" by an antibody, and eventually get eliminated through normal process. If they are still "active", they float until they encounter a b-cell or a cd-4 t-cell. Encountering a b-cell is good, encountering a cd-4 t-cell is bad.

Without meds the immune system could not handle all this by itself, and there would be exhaustion, which is what we've seen where people only had 10 years to live, the last few years being when there was no immune system left to treat an opportunistic infection.

With meds, we can disturb the virus well enough so that it finally cannot replicate anymore. The problem is that there are places where the meds don't go, and it is thought that there are viruses in those places that are latent, just waiting to be released, and bham here we go again when they're back in the normal blood flow.

There is also the problem of cd-4 t-cells that are disappearing even though they're not infected, and this is being studied too.

So to recap the different types of cells:

b-cells: bind to viruses eat them and change their internal identification in that process.cd-4 t-cells: recognize that there is an identification problem with the b-cel, bind to the b-cell, which switches the b-cell into creating antibodies mode.cd-8 t-cells: get alerted by this, and they kill infected b-cells after their job is done by releasing proteins that make the b-cell die.cd-3: an accessory to cd-4 and cd-8 t-cells that allow those cells to be identified as cd-4 or cd-8.

That's a good explanation there, milker. Well done! I'd love to be able to figure out how to translate this type of explanation into something akin to the soldiers and generals story that I put up above...because I'd like to become adept at putting this process into an easily understood form that just about anybody can picture in their minds. It's a bit easier for us because we are already familiar with the verbage of all this. That's something for me to try to figure out, though any help from anyone would be welcomed. I'd like to develop a form of explaining all this that got the steps right, but wasn't quite so "clinical". I guess I'm saying that I am interested in developing something akin to HIV for Dummies- something that any high school (or even middle school) age kid could pick up and get really in the know about HIV without getting scared off by the terminology.

I'm not very army savvy but I agree with you in trying to get an explanation that everyone can understand. Mine is getting there I think but if you can use better analogy (did I say anal?) that would be great! And you should verify that what i'm saying is actually correct!

yeah. again, we'll just see what we learn over the course of this thread and beyond. i think you gave a good explanation. I just want to try to learn how to distill this information into lay terms.

I used to assist in teaching a simplified HIV education course to some people with developmental disabilities. (Shoulda listened to my own lessons, eh?) That is where the seed for this kind of approach got planted in my head.

Bob the B-cell doesn't like Victor and eats it. But after Bob eats Victor, it becomes pregnant! and Bob starts making little Victor babies! Charles the Disease fighter from Disease station 4 is alerted and holds Bob tight so that Bob stops making babies.Bob feels better and transforms into Blaster the super hero.Blaster blasts Victor babies with its BlasterGun!Charles the Disease Fighter calls Connie the Disease killer from station 8.Connie kills Blaster because Blaster, previously Bob, is sick.

Great explanations Milker and Thunter -- I have the same understanding. I agree a more "lay" (I said it!! LAY LAY LAY LAY LAY) explanation...I will put my thinking cap on too.

I have a question which I believe is on topic or at least in the relm (NO -- I don't play Dungeons and Dragons just if you were wondering after using relm -- well if I was roll-playing in a leather scene...hmmmm hmmmm -- SORRY, just woke up and the mind is a wondering).

We have touched on the HIV havens like the brain and balls...Here is the thing -- (I may not be looking in the right spot for research);

I understand that in these areas meds have a hard time penetrating thereby the virus is free the replicate...That said here are the questions;

Is my understanding correct that disease is only replicating in these havens and latent when it comes to actively destroying cells?So, are these replicated cells just waiting to release all at the same time into the rest of the body? (Does this mean my balls will explode? JUST JOKING)

Hon, I don't know. Not the foggisest. Good questions, though. "Let's start here" suggests to me you've got a few more questions in cue.

I'm a little hung on your question, "Is disease only replicating in these havens and latent when it comes to actively destroying cells?" Disease? You mean virus, right? It sounds to me like, if there is replicatioin going on, there is cell damage going on. That damage is just contained in these hidey-holes out of rech of the meds. I do know that this virus has a very long latency period. It can hang around without doing anything for a long time- years, I believe?

My guess is that the scenario might be something like this: (Let's pick the nuts since it's a funner location) The virus is able to replicate in the nuts where the meds can't reach as well. Some of the infected cells make their way out of that neighborhood and float around in the rest of the system. It spouts out some other viral copies, but those don't get anywhere because they are now in areas the meds can reach. These smaller number of viral copies floating around now would perhaps account for the <50 amount that are circulating in the system.

Another study published here (but I cant find it) says the viral load is lower in the CNS fluid than in the blood stream. So if you are undetectable (below 50 copies) the numbber of copies in the brain is even lower. That is why aids related dementia is somethig from the past.My "boyfriend???" has been on treatment since 1992 and has been undetectable since the first viral load tests. He has never developed any resistance to meds and is taking combivir and viread. Only 3 pills a day.

Don't make a common mistake and think that a HIV "Tora Bora" is merely an organ or body part that drugs can not reach. The answer could be more subtle than that. The way you are talking about blood makes me wonder if you have considered that blood and the immune system are actually made up of a variety of cells - all of which have different susceptibilities to HIV. OK, only cells that express HIV receptors are going to be reservoirs, but these are actually not limited to CD4 T-cells. In addition to the areas you are considering, there are cell types within organs and areas that might harbor HIV that also don't take up drug very well. This makes the latent and persistent pools everywhere. Put another way, drug can get to that location but not to the certain cells within that location. You might find drug flooding the area - except at a cellular level it wouldn't be where it was needed.

R

« Last Edit: March 27, 2007, 09:05:29 PM by HIVworker »

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

I'm not sure i understand very well what you're saying. Are you saying that there is no specific place where the drugs cannot reach the HIV but that the drug is not "flooding" enough areas to hit every cell that might be infected, or are you saying that everywhere in the body there are places that are not particularly of interest to the virus, however it's there, but the drugs can't penetrate the tissues where the virus is located?

What I am trying to point out is that although the drug can be in the blood, it is a mistake to say that all cells in the blood can take up drug equally. The persistent pools of HIV replication might be in organs of the body like the brain that don't allow many drugs in as you have been discussing, but it could also be true that there are cells in areas where drugs can go that don't take up enough drug to be protected. So the persistent pool could be cell types in areas where drugs can go that aren't able to take up enough drug to be protected.

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

1) not every cell will necessarily react to the drug, so those could still be used by the virus to replicate.2) there are areas like the brain that are difficult to reach by some drugs, and the virus could be replicating in there.3) even if an area can be reached by a drug, the amount of it may not be enough to be effective.

4) If drug can get to an area there might be some cells in that location that, unlike all the other cells, do not take up drug and will be reservoirs for replication.

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

...i think there is still a huge bias against gay male sex as opposed to st8t sex, for example, st8ts live swim in a world of love being the glue of thier culture, a man loves a woman visa versa and even though one is poz other neg, they stick together and scientists now prove they dont transmit even if they have sex without a condom in order to create a baby, (personally if i was neg i would be afraid, but the point is love, they love and want to have baby with that person)...

...gays swim, live in a world of sex, where love is infinately less important, so now we have all these fear campaigns

Yes, absolutely. And we all have our own individual prejudices about promiscuity, sex in love, love before sex, prostitution, dull relationships, etc. etc. We poz are supposed to warn the world like lepers; "Unclean. Unclean." We are living way too long and way too healthy not to be at risk of infecting others, years after our own sero-conversion. It's everyone's responsibility. Morality is great. Moralism kills.

Scientists and policy-makers should stay clear of moral judgments and simply try to reduce the risks of transmission among all the myriad of ways and reasons people "couple" for sex. The old "safe sex" list is nearly (i.e., the emphasis on condom use on this Site is correct) useless.

I don't think scientists are making moral judgements. How their results are reported in the media is a different thing. I've seen a study on the Env of HIV in newly transmitted virus in serodiscordant couples be used as evidence that condoms don't work (they told patients to use condoms and still got transmission....a word from the author revealed that they found sperm in the vagina's of many patients indicating that even though they were given condoms and they said they used them, they clearly weren't). Scientist is reporting the methodology of the study and it gets warped into saying something it isn't.

R

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NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Interesting discussion. The current commercially available viral load assays measure viral particles in plasma, the liquid fraction of the blood that does not contain any cells. Thus, even though viral replication occurs inside cells, the assay measures the concentration of the virus in plasma that have not attached to a host cell. Only 2% of T cells circulate in blood. The rest are in lymph nodes, spleen and other lymph glands. So while easily accessible, in untreated individuals, the viral load in the blood may not exactly represent what is going on in other organs or cells. In research settings, viral load in sites other than blood plasma have been measured, such as lymph nodes, actual blood cells (rather than plasma), semen, vaginal washings, cerebrospinal fluid, etc. They are useful in research but not clinically. It does appear that with antiretroviral treatment, the drop in viral load in tissues (especially the lymph tissues) correlates with that of plasma viral load drop making the plasma measurement a readily accessible marker for treatment response.

So what exactly does plasma viral load indicate? It is basically a measure of one’s viral burden. Without treatment, the viral burden in plasma during chronic infection represents the tug-o-war between the body’s defenses against the virus and the virus’ ability to multiply. Free floating viruses have to attach to a host cell in order to remain viable; otherwise, they are cleared from the body by the immune system. This is the same immune system that tries to rid of the infected cells. The tricky part is the main target cells (T-cell) are these very same immune cells that are supposed to orchestrate the clearance of the virus. Thus, it becomes a dicey situation when these very cells that try to control the virus are themselves being targeted, rendered useless with immune fighting, and eventually hijacked by the virus to produce more viruses. It is still a mystery as to why in the absence of treatment, there are a few people who are actually able to get their virus under control by their own immune system defenses (thus, the LTNP).

Infected T-cells that literally get transformed into HIV-producing factories are the target of currently available antiretroviral meds. By interrupting the HIV life-cycle in these cells at various points with combination antiretrovirals, production of new viable virus gets shut down. These allow new uninfected T-cells to regenerate and repopulate (thus leading to CD4 count recovery). Those cells that are already infected and shut down eventually die (active T-cells, irrespective of whether or not they are infected, do have a finite life span; but the HIV-infected ones that are not resting tend to die quicker due in part to stimulation and faster programmed cell death).

There are also “resting” T-cells that get infected but are not actively replicating. These cells do not contribute to the viral load burden. No one knows for sure how long these cells live, but some estimates are in years. Current drugs do not affect these because they are not yet activated. However, they can be a potential source of persistence and re-emergence if treatment is stopped and they get activated at some point.

So why not a viral load target of 10 or 1 instead of 50? It’s mainly because the lower viral load have not really been proven clinically relevant as an improved treatment response compared to the 50 cut-off. There are research assays that do go to these lower limits of detection but their utility in clinical practice is unproven. Plus, as it is now, there are people who have difficulty achieving a VL <50 on treatment and have persistent, but low detectable viral loads (low hundreds). Clinicians don’t exactly know what to do in these situations now. To lower the viral load cut-off even more would compound this problem without necessarily improving treatment outcome. That is, someone on treatment who reaches a <10 VL may not necessarily achieve a better outcome than someone whose VL is persistently between 11-49 (both are <50).

Finally, it has already been mentioned that even a plasma viral load of “zero” does not mean that the virus has been eradicated. So going after lower and lower cut-offs may not really mean a whole lot clinically with currently available treatments that cannot eradicate the virus.

I'm a little hung on your question, "Is disease only replicating in these havens and latent when it comes to actively destroying cells?" Disease? You mean virus, right? It sounds to me like, if there is replicatioin going on, there is cell damage going on. That damage is just contained in these hidey-holes out of rech of the meds. I do know that this virus has a very long latency period. It can hang around without doing anything for a long time- years, I believe?

I think we need to clarify "latency" when the term is used. There are a couple of interpretations in that regard that may be used interchangeably but may not mean the same thing. For instance, when Tim said "I do know that this virus has a long latency period" this may refer to latent period of the disease, which is defined as the period between acquiring the infection and manifesting symptoms (specifically, symptoms related to immune deficiency). In this regard, even though the "latent period" is long, it does not mean that the disease is inactive. It is going through its course wreaking havoc to the immune system but remains clinically silent without treatment until the first symptoms of immune deficiency occur. It also does not mean that because one is in the latent period of the disease, that medications would not make a difference. In fact, starting antiretrovirals even before one gets symptoms of immune deficiency is important to keep one from getting immune deficient.

The other latency referred to here is in regard to latent viral reservoirs, which refers more to those cells that have HIV genetic material already incorporated but are otherwise resting or inactive (or very slowly replicating). These would include resting T-cells residing in the lymph tissues and other organs, as well as other cells that get infected but are not necessarily used as HIV factories. These are the ones that current medications cannot reach. Furthermore, some are shielded from the meds because they reside in organs that are not easy to reach with drugs due to some kind of barrier (blood-brain barrier; blood-testis barrier). When one achieves viral suppression during treatment, by minimizing viral replication, the T-cells have a chance to repopulate (because they are not under constant threat of viral attack). When treatment gets interrupted, any of these reservoirs can re-start the process of releasing active virus that can infect the T-cells once again, which can then get converted to virus-producing factories all over again. These reservoirs are not as plentiful as the non-resting T-cells and exists even as the other T-cells get infected with and succumb to the virus. They are very important nonetheless in terms of 1) the inability of current treatments to "cure" HIV, and 2) their role in making drug resistant mutations that emerge quite permanent.

It also does not mean that replication = cell destruction. This may be true of the infected activated T-cells but may not be true of other reservoir cells. In fact, even at an undetectable (<50) viral load, there is still some residual viral replication going on. This is still the subject of active research in terms of what this means clinically.